Here are some things I think more primary care doctors and pharmacists should be aware of:
Codeine is a terrible painkiller
If you view it primarily as a pro-drug. "Roughly" 5-10% of the dose being converted to morphine. The enzyme responsible for this is CYP2D6 – a randomised control trial of 96 children given codeine 1.5mg/kg or morphine 0.5mg/kg found that morphine and its metabolites were not detectable in 36% of the codeine group. The Codeine group required rescue analgesia at 1 and 4 hours more often (1). "Polymorphisms in CYP2D6 mean that codeine is ineffective as an analgesic for approximately 10% of the white population" (2).
ALL the SSRI's (Sertraline, Fluoxetine, Paroxetine) are known to inhibit CYP2D6 – this reduces the conversion of codeine to morphine. This is one example. CYP2D6 is "involved in the metabolism of approximately 20% of drugs in clinical use" (3).
TRAMADOL IS ALSO AN SNRI – treat it as such. It has a risk profile similar to Buproprion (Wellbutrin) in regards to seizure risk and problems with rapid cessation (no source may be wrong)
It acts on the mu-opioid receptor (μ), as well as reuptake inhibition of the monoamines norepinephrine (NE) and serotonin (5HT). Dual action antidepressants mirtazapine, duloxetine, and most notably venlafaxine (Effexor), which tramadol is closely related to in structure, also inhibit NE and 5HT reuptake." (4)
Source: Original link